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A Phase 2 Study of Triapine® (NSC #663249) and Cisplatin in Combination With Pelvic Radiation for Treatment of Stage IB2-IVa Cervical Cancer or Stage II-IV Vaginal Cancer


Phase 2
18 Years
N/A
Not Enrolling
Female
Recurrent Cervical Cancer, Recurrent Vaginal Cancer, Stage IB Cervical Cancer, Stage II Vaginal Cancer, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage III Cervical Cancer, Stage III Vaginal Cancer, Stage IVA Cervical Cancer, Stage IVA Vaginal Cancer, Stage IVB Cervical Cancer, Stage IVB Vaginal Cancer, Therapy-related Toxicity

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Trial Information

A Phase 2 Study of Triapine® (NSC #663249) and Cisplatin in Combination With Pelvic Radiation for Treatment of Stage IB2-IVa Cervical Cancer or Stage II-IV Vaginal Cancer


PRIMARY OBJECTIVES:

I. To determine three-month fasting F-18 fluorodeoxyglucose (FDG) positron emission
tomography (PET/CT) imaging complete metabolic response as defined by the European
Organization for Research and Treatment of Cancer (EORTC) PET study group.

SECONDARY OBJECTIVES:

I. To determine 6-month progression-free survival rate as calculated from the date of first
treatment until date of disease progression, relapse, or death.

II. To quantitate change in pre-treatment standard uptake value (SUV) on PET/CT and
post-treatment PET/CT or disease progression PET/CT.

III. To quantitate pre-treatment, during treatment and 3-mo post-treatment grade 2 or higher
gastrointestinal, genitourinary, and sexual function toxicity resulting from Triapine®,
cisplatin, and radiation therapy as measured by CTCAE v3.0, which will be utilized until
December 31, 2010; CTCAE v4.0 will be utilized beginning January 1, 2011.

IV. To associate smoking habit (non-smoker, smoker who quit during therapy, smoker) with
3-mo post-treatment PET/CT metabolic response and 3-mo best overall clinical response as
measured by RECIST criteria after Triapine®, cisplatin, and radiation therapy.

V. To associate HPV or non-HPV sub-type cervical cancer with 3-mo post-treatment PET/CT
metabolic response and 3-mo best overall clinical response as measured by RECIST criteria
after Triapine®, cisplatin, and radiation therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to brachytherapy
treatment (planned intracavitary brachytherapy vs none).

Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, and 30 and triapine IV
on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Patients also undergo
pelvic external beam radiotherapy 5 days a week during weeks 1-5. Patients may undergo
parametrial boost radiation and intracavitary low-dose or high-dose rate brachytherapy as
clinically indicated.

Patients undergo whole-body F-18 fluorodeoxyglucose-PET/CT imaging at baseline, at 3 months
after completion of study treatment, and at disease progression. Patients complete Sexual
Function-Vaginal Changes Questionnaire and a smoking behavior questionnaire at baseline, at
3 months after completion of study treatment, and at disease progression.

After completion of study treatment, patients are followed periodically for up to 5 years.


Inclusion Criteria:



- Female patients must have histologically confirmed (tumor tissue biopsy) primary
clinical stage IB2-IVB cervical cancer or clinical stage II-IVB vaginal cancer not
amenable to curative surgical resection alone to be eligible; patients with stage IVB
cervical cancer may receive systemic chemotherapy for treatment of metastatic disease
a) after the 3-month post-therapy PET scan and b) if the 3-month post-therapy PET
scan documents progressive disease at the discretion of the treating physician

- Patients with other active invasive malignancies are excluded; patients with prior
malignancies (except non-melanoma skin cancer or prior in situ carcinoma of the
cervix, patients with synchronous or past history of primary endometrial cancer
meeting all conditions of a) stage not greater than IB, b) no more than superficial
myometrial invasion, c) without vascular or lymphatic invasion, and d) no poorly
differentiated subtypes including papillary serous, clear cell or other FIGO grade 3
lesions; patients with other invasive malignancies who had (or have) cancer present
within the last five years are excluded; patients are excluded if they have received
prior low abdominal or pelvic radiotherapy for any reason that would contribute
radiation dose that would exceed tolerance of normal tissues

- Life expectancy of greater than 3 months

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Hemoglobin >= 10 g/dL

- Total bilirubin =< 2.0 mg/dL

- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

- PT/aPTT =< 1.5 X institutional upper limit of normal

- Patients should have a serum creatinine =< 1.5mg/dL to receive weekly intravenous
cisplatin chemotherapy

- Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for
cisplatin chemotherapy if the estimated creatinine clearance is >= 30 ml/min;
patients eligible for cisplatin chemotherapy using the criteria for creatinine
clearance may also receive intravenous Triapine®

- Women of child-bearing potential and male partners must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation; should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately

- Patients must demonstrate ability to understand and the willingness to sign a written
informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier
are excluded

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive
neurological dysfunction that would confound the evaluation of neurological and other
adverse events

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Triapine® or other agents used in study

- Patients unable to receive intravenous chemotherapies as a consequence of poor
vascular access are ineligible

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, known inadequately controlled hypertension, significant pulmonary disease
including dyspnea at rest, patients requiring supplemental oxygen, or poor pulmonary
reserve; proteinuria or clinically significant renal function impairment (baseline
serum creatinine > 2mg/dL), or psychiatric illness/social situations that would limit
compliance with study requirements are excluded

- Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded
as the antidote methylene blue for Triapine® toxicity may be at best ineffective in
such patients and may have the potential to complicate the clinical situation by
provoking hemolysis

- Pregnant women are excluded from this study because Triapine® is a heterocyclic
carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient
effects; screening beta-hcg levels and diagnostic tests will be used to determine
eligibility; because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with Triapine®, breastfeeding
should be discontinued if the mother is treated with Triapine®; these potential risks
may also apply to other agents used in this study

- Patients not willing to agree to use appropriate contraception while on trial will be
excluded

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with Triapine®; in addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy; appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated; HIV testing is not
mandatory; patients that are known to be HIV-positive are ineligible if they are
receiving combination antiretroviral therapy

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Fasting F-18 Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET/CT) Imaging Complete Metabolic Response, Reported Following National Cancer Institute (NCI) and European Organization for Research and Treatment of Cancer (EORTC) Guidelines.

Outcome Description:

To quantitate change in pre-treatment standard uptake value (SUV) on PET/CT and posttreatment PET/CT or disease progression PET/CT. Change in PET/CT SUV will be associated with 3-month best overall clinical response.

Outcome Time Frame:

post therapy at 3 months

Safety Issue:

No

Principal Investigator

Charles Kunos

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Western Reserve University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02896

NCT ID:

NCT00941070

Start Date:

July 2009

Completion Date:

Related Keywords:

  • Recurrent Cervical Cancer
  • Recurrent Vaginal Cancer
  • Stage IB Cervical Cancer
  • Stage II Vaginal Cancer
  • Stage IIA Cervical Cancer
  • Stage IIB Cervical Cancer
  • Stage III Cervical Cancer
  • Stage III Vaginal Cancer
  • Stage IVA Cervical Cancer
  • Stage IVA Vaginal Cancer
  • Stage IVB Cervical Cancer
  • Stage IVB Vaginal Cancer
  • Therapy-related Toxicity
  • Uterine Cervical Neoplasms
  • Vaginal Neoplasms

Name

Location

Case Western Reserve UniversityCleveland, Ohio  44106